The present invention relates to the production of lipid vesicles using an anionic material as the primary lipid in the vesicle walls. More particularly, a neutralized ester in the form of a monomeric or dimeric alkyd is used to form lipid vesicles.
A substantial number of different materials are described in the literature as being useful to form lipid vesicles. The first lipid vesicles, called liposomes, used phospholipid materials such as phosphatidyl choline as the primary structural lipid. Most of these phospholipids are dual chain zwitterions. Several cationic materials such as quaternary ammonium compounds and certain betaines have also been tried. More recently, non-ionic materials such polyoxyethylene ethers and esters have been used successfully to form lipid vesicles by both L'Oreal and Micro Vesicular Systems. While these non-ionic materials have certain advantages compared with phospholipids and quaternary ammonium compounds in terms of cost and the ability to be used in very rapid vesicle forming processes, it is occasionally Preferred to use a charged vesicle former.
There are few reports of anionic materials being successful as lipid vesicle forming materials. Micro Vesicular Systems has used sarcosinates to form vesicles; however, these materials will only form vesicles at non-neutral pH. In addition, there are reports of the use of certain fatty acids to form vesicles, e.g., the so-called "ufasomes," but these vesicles do not appear to be particularly stable. In addition, the processes described for making of ufasomes are very slow.
The most common industrial use of anionic materials having large fatty acid chains are in the formation of polyesters such as nylon, dacron, and the alkyds used in the paint industry. All of these polyesters have a highly polymerized structure, either as linear polymers, e.g., nylon fibers, or as a highly cross-linked structure, e.g., the laquers or alkyd resins used in the paint industry. Polymerization proceeds rapidly with these materials. Because the polymers have been so important industrially, there has been little work with the monomeric forms of these materials.
The alkyds used in the paint industry are normally made in a two step, three component, reaction. First, a fatty acid, preferably a C.sub.16 -C.sub.18 fatty acid, is reacted with a polyol such as glycerol or pentaerythitol to form a monoglycercide. This monoglyceride is then reacted with a dianhydride such as phthalic, isophthalic, or trimellitic anhydride under conditions whereby polymerization takes place. These highly polymerized molecules, called alkyds, are used to act as the sealer in oil based paints. These alkyds are soluble in certain oils and organic solvents (but not in water) so they are used only in the oil based paints. However, these alkyds are not used in the monomeric or dimeric form since the polymerized form, which is highly cross-linked, is necessary for a long lasting finish. In fact, until the present invention, these alkyds have not been considered for use as vesicle formers.
Accordingly, an object of the invention is to provide lipid vesicles, and a method of making lipid vesicles, using anionic esters such as alkyds.
Another object of the invention is to provide anionic vesicles without adding a separate charge-producing agent.
A further object of the invention is to provide pH sensitive vesicles using materials which will form vesicles at neutral or higher pH while disintegrating at acid pH.
These and other objects and features of the invention will be apparent from the following description.